Biology Reference
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unlike those in T cells ( Ugolini et al., 1997). Chirmule et al. have reported
that the carboxy terminus part of gp41 also has B-cell stimulatory activity
(Chirmule et al., 1990). Macchia et al. have shown that membrane-associated
TNF-a expressed by HIV-infected T cells is also involved in maintaining B-cell
activation (Macchia et al., 1993).
The sustained GC hyperplasia observed in HIV-infected patients may be
partially accounted for by the continuous production of virions and viral pro-
teins within the lymphoid tissue. Highly infectious HIV-1 virions have been
shown to be present in immune complexes expressed by FDC (Armstrong and
Horne, 1984; Heath et al., 1995; Joling et al., 1993; Schacker et al., 2000) and to
persist, to a lower extent, under antiretroviral tritherapy (Morris et al., 1998).
CD21 mAb may be useful for releasing immune complexes from FDC ( Kacani
et al., 2000). However, the maintenance of follicular hyperplasia during the
chronic phase of the disease suggests that variations in gp120/160 proteins in-
duce the recruitment of naive B cells directed against new antigenic epitopes.
During other chronic infections, as B cells encounter the same Ag, the GC re-
action is weak and renewal of the memory pool limited. Alternatively, gp120
acting, as a superantigen, and HIV-1 accessory proteins (Tat, vpr), penetrating
into uninfected cells, may be involved in the abnormal B-cell activation ob-
served in HIV
patients. We have recently shown that Tat impairs the pro-
liferative response of B cells to various stimuli and their Ig production in vitro
( Lefevre et al., 1999).
INFECTION OF B CELLS: IN VITRO ARTIFACT OR REALITY?
The infection of B lymphocytes by HIV-1 was ®rst described in B-cell lines
(Casareale et al., 1984; Gras and Dormont, 1991; Laurence and Astrin, 1991;
Robinson et al, 1998; Rodriguez-Alfageme et al., 1998) and then in primary
HIV-negative B cells subjected to in vitro infection (Gras et al., 1999; Moir
et al., 1999; Poulin et al., 1994). In our hands, the HIV-1 infection of primary
tonsilar B cells is complement- and virusÐspeci®c Ab-dependent (C
0
-ADE
infection) and involves the complement receptors 2 (CD21) and 1 (CD35) and
CD4 antigen (Gras et al., 1993; Legendre et al., 1996). If C3-de®cient comple-
ment or normal serum is used instead of HIV
serum, no B-cell infection occurs.
Similarly, mAb directed against CD21, CD35, or CD4 antigens and the CD4-
HSA recombinant protein inhibit p24 production in B-cell cultures (Legendre
et al., 1996). Although weak (<1000 molecules per cell as assessed by quanti-
tative ¯ow cytometry), the expression of CD4 at the surface of human B cells
has also been reported by others, as well as the involvement of this antigen in
the HIV-1 infection of B cells ( Fritsch et al., 1998; Moir et al., 1999; Zhang and
Henderson, 1994). On B cells, CD21 participates in two mutually exclusive
complexes: one including CD19, CD81, and Leu 13 and the second including
CD35 ( Tedder et al., 1997; Tuveson et al., 1991). CD21 mAb and CD35 mAb
strongly inhibit p24 production, whereas CD19 mAb does not, suggesting that
